title: Population pharmacokinetics of ampicillin and sulbactam in patients with community-acquired pneumonia: evaluation of the impact of renal impairment.
abstract: OBJECTIVE
  The aims of this study were to develop a population pharmacokinetic (PK) model of ampicillin and sulbactam, to identify patient characteristics influencing the PK, and to explore the relationship between dose regimen and degree of renal impairment with exposure and time above minimum inhibitory concentration (MIC).
  
  
  METHODS
  This analysis was performed on PK data for ampicillin and sulbactam and MIC data from a clinical trial in Japanese patients with community acquired pneumonia. Simulations were performed to investigate the effects of different dosing intervals on exposure and time above MIC in various degrees of renal impairment.
  
  
  RESULTS
  The plasma concentrations from 47 patients were adequately described by a two compartment model with simultaneous fit of ampicillin and sulbactam PK data, where creatinine clearance on clearance and body weight on volume in the peripheral compartment were identified as covariates for both drugs. Creatinine clearance contributed to reducing inter-individual variability of clearance by 16%. Mean clearance (inter-individual variability) for ampicillin and sulbactam was estimated to be 10.7 l h(-1) (14.8%) and 10.4 l h(-1) (15.2%), respectively. The time above MIC for each pathogen was generally > 50% of the treatment period. Simulations for exposure and time above MIC supported currently recommended dose adjustments.
  
  
  CONCLUSIONS
  This study provided a PK model for ampicillin and sulbactam, the time above MICs for identified pathogens and associated simulation results. These findings provide useful information and augment evidence for the established dosage regimens in patients with various degrees of renal impairment.
authors.affiliation: Pharmacometrics, Pfizer Global Research and Development, Sandwich, Kent, UK.
authors.forename: Elena
authors.initials: E
authors.lastname: Soto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shoji
authors.forename: Chieko
authors.initials: C
authors.lastname: Muto
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Tomono
authors.forename: Scott
authors.initials: S
authors.lastname: Marshall
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000667:Ampicillin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D017714:Community-Acquired Infections / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D003198:Computer Simulation; D004334:Drug Administration Schedule; D004338:Drug Combinations; D054796:Drug Dosage Calculations; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007564:Japan; D007668:Kidney / Q000503:physiopathology*; D007674:Kidney Diseases / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D008297:Male; D008657:Metabolic Clearance Rate; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008954:Models, Biological; D018410:Pneumonia, Bacterial / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D013407:Sulbactam / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D000667:Ampicillin; D013407:Sulbactam
keywords: Unasyn; ampicillin; pneumonia; population pharmacokinetics; sulbactam